U.S. Pat. No. 4,959,356, issued Sep. 25, 1990, inventors Miura and Gabel describe boronated porphyrin compounds for use in boron neutron capture theory (BNCT). Similar compounds are discussed in an article by Miura et al. Tetrahedron Letters, Vol. 31, No. 16, pp. 2247-2250 (1990). The boronated porphyrins described by Miura have vinyl carborane moieties and are reported to be water insoluble. Thus the borane cages must be opened to obtain water solubility. But by opening those borane cages, one encounters significantly more toxicity for the compounds. Moreover, the resultant open-cage compounds are still not sufficiently water soluble to enable administration without the use of adjuvant substances (e.g., polyethylene glycol). Also the compounds which Miura et al. describe are (at most) 19% boron by weight in the physiologically useful (K.sup.+ -salt) form. This is a disadvantage since limiting human doses may well be determined by the amount of porphyrin unit doses which may be tolerated.
In addition to neutron capture therapy (NCT) generally and boron neutron capture therapy (BNCT) more specifically, additional uses of porphyrins in cancer therapies are those therapeutic strategies generally referred to as photodynamic therapy (PDT). A review article by Delaney and Glatstein in Comprehensive Therapy, pp. 43-55 (May 1988) describes this therapeutic strategy where a light-activated photosynthesizer can interact with ground state molecular oxygen to yield reactive oxygen species (via singlet oxygen). Since porphyrins of many structural types localize in a wide variety of malignant tumors, this localization has formed the basis for treatment of at least 3000 patients in the United States alone (twice that worldwide) over the past several years through PDT. Complete response (disappearance of tumor or biopsy proven) has occurred in a high percentage of patients in relatively advanced stages of skin, bladder, and lung cancers, and cancers of the reproductive system through photodynamic therapy.
U.S. Pat. No. 5,109,016, issued Apr. 28, 1992, inventors Dixon et al., describes compositions said to inhibit replication of human immunodeficiency virus by porphyrin and certain porphyrin-like compounds. These compounds were tested for inhibition of reverse transcriptase as a screening method to determine inhibition of HIV; however, during the 8th International Conference on AIDS, held in late July, 1992, in Amsterdam, some presentations suggested that many drugs that showed initial promise against HIV-1 have been found to have serious shortcomings because HIV-1 rapidly becomes resistant to the so-called "non-nucleoside reverse transcriptase inhibitors." See, C&EN, 70:34, pp. 26-31 (Aug. 24, 1992). As an example of a non-nucleoside derivative that binds to a site other than the active site (non-competitive inhibition), see Pauwels et al., Nature, 343, pp. 470-474 (1990); however, resistance develops rapidly to this derivative.